TY - JOUR A1 - Radbruch, Moritz A1 - Pischon, Hannah A1 - Ostrowski, Anja A1 - Volz, Pierre A1 - Brodwolf, Robert A1 - Neumann, Falko A1 - Unbehauen, Michael A1 - Kleuser, Burkhard A1 - Haag, Rainer A1 - Ma, Nan A1 - Alexiev, Ulrike A1 - Mundhenk, Lars A1 - Gruber, Achim D. T1 - Dendritic core-multishell nanocarriers in murine models of healthy and atopic skin JF - Nanoscale Research Letters N2 - Dendritic hPG-amid-C18-mPEG core-multishell nanocarriers (CMS) represent a novel class of unimolecular micelles that hold great potential as drug transporters, e. g., to facilitate topical therapy in skin diseases. Atopic dermatitis is among the most common inflammatory skin disorders with complex barrier alterations which may affect the efficacy of topical treatment. Here, we tested the penetration behavior and identified target structures of unloaded CMS after topical administration in healthy mice and in mice with oxazolone-induced atopic dermatitis. We further examined whole body distribution and possible systemic side effects after simulating high dosage dermal penetration by subcutaneous injection. Following topical administration, CMS accumulated in the stratum corneum without penetration into deeper viable epidermal layers. The same was observed in atopic dermatitis mice, indicating that barrier alterations in atopic dermatitis had no influence on the penetration of CMS. Following subcutaneous injection, CMS were deposited in the regional lymph nodes as well as in liver, spleen, lung, and kidney. However, in vitro toxicity tests, clinical data, and morphometry-assisted histopathological analyses yielded no evidence of any toxic or otherwise adverse local or systemic effects of CMS, nor did they affect the severity or course of atopic dermatitis. Taken together, CMS accumulate in the stratum corneum in both healthy and inflammatory skin and appear to be highly biocompatible in the mouse even under conditions of atopic dermatitis and thus could potentially serve to create a depot for anti-inflammatory drugs in the skin. KW - CMS KW - Skin KW - Topical treatment KW - Dermal delivery KW - Atopic dermatitis KW - Oxazolone KW - Fluorescence lifetime imaging microscopy KW - Nanomaterials KW - Multi-domain nanoparticles KW - Penetration enhancement Y1 - 2017 U6 - https://doi.org/10.1186/s11671-017-1835-0 SN - 1556-276X VL - 12 IS - 64 PB - Springer CY - New York ER - TY - GEN A1 - Radbruch, Moritz A1 - Pischon, Hannah A1 - Ostrowski, Anja A1 - Volz, Pierre A1 - Brodwolf, Robert A1 - Neumann, Falko A1 - Unbehauen, Michael A1 - Kleuser, Burkhard A1 - Haag, Rainer A1 - Ma, Nan A1 - Alexiev, Ulrike A1 - Mundhenk, Lars A1 - Gruber, Achim D. T1 - Dendritic core-multishell nanocarriers in murine models of healthy and atopic skin T2 - Postprints der Universität Potsdam Mathematisch-Naturwissenschaftliche Reihe N2 - Dendritic hPG-amid-C18-mPEG core-multishell nanocarriers (CMS) represent a novel class of unimolecular micelles that hold great potential as drug transporters, e. g., to facilitate topical therapy in skin diseases. Atopic dermatitis is among the most common inflammatory skin disorders with complex barrier alterations which may affect the efficacy of topical treatment. Here, we tested the penetration behavior and identified target structures of unloaded CMS after topical administration in healthy mice and in mice with oxazolone-induced atopic dermatitis. We further examined whole body distribution and possible systemic side effects after simulating high dosage dermal penetration by subcutaneous injection. Following topical administration, CMS accumulated in the stratum corneum without penetration into deeper viable epidermal layers. The same was observed in atopic dermatitis mice, indicating that barrier alterations in atopic dermatitis had no influence on the penetration of CMS. Following subcutaneous injection, CMS were deposited in the regional lymph nodes as well as in liver, spleen, lung, and kidney. However, in vitro toxicity tests, clinical data, and morphometry-assisted histopathological analyses yielded no evidence of any toxic or otherwise adverse local or systemic effects of CMS, nor did they affect the severity or course of atopic dermatitis. Taken together, CMS accumulate in the stratum corneum in both healthy and inflammatory skin and appear to be highly biocompatible in the mouse even under conditions of atopic dermatitis and thus could potentially serve to create a depot for anti-inflammatory drugs in the skin. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 724 KW - CMS KW - skin KW - topical treatment KW - dermal delivery KW - atopic dermatitis KW - oxazolone KW - fluorescence lifetime imaging microscopy KW - nanomaterials KW - multi-domain nanoparticles KW - penetration enhancement Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-430136 SN - 1866-8372 IS - 724 ER - TY - JOUR A1 - Wanjiku, Barbara A1 - Yamamoto, Kenji A1 - Klossek, Andre A1 - Schumacher, Fabian A1 - Pischon, Hannah A1 - Mundhenk, Lars A1 - Rancan, Fiorenza A1 - Judd, Martyna M. A1 - Ahmed, Muniruddin A1 - Zoschke, Christian A1 - Kleuser, Burkhard A1 - Rühl, Eckart A1 - Schäfer-Korting, Monika T1 - Qualifying X-ray and Stimulated Raman Spectromicroscopy for Mapping Cutaneous Drug Penetration JF - Analytical chemistry N2 - Research on topical drug delivery relies on reconstructed human skin (RHS) in addition to ex vivo human and animal skin, each with specific physiological features. Here, we compared the penetration of dexamethasone from an ethanolic hydroxyethyl cellulose gel into ex vivo human skin, murine skin, and RHS. For comprehensive insights into skin morphology and penetration enhancing mechanisms, scanning transmission X-ray microscopy (STXM), liquid chromatography tandem mass spectrometry (LC-MS/MS), and stimulated Raman spectromicroscopy (SRS) were combined. STXM offers high spatial resolution with label-free drug detection and is therefore sensitive to tissue damage. Despite differences in sample preparation and data analysis, the amounts of dexamethasone in RHS, detected and quantified by STXM and LC-MS/MS, were very similar and increased during the first 100 min of exposure. SRS revealed interactions between the gel and the stratum corneum or, more specifically, its protein and lipid structures. Similar to both types of ex vivo skin, higher protein-to-lipid ratios within the stratum corneum of RHS indicated reduced lipid amounts after 30 min of ethanol exposure. Extended ethanol exposure led to a continued reduction of lipids in the ex vivo matrixes, while protein integrity appeared to be compromised in RHS, which led to declining protein signals. In conclusion, LC-MS/MS proved the predictive capability of STXM for label-free drug detection. Combining STXM with SRS precisely dissected the penetration enhancing effects of ethanol. Further studies on topical drug delivery should consider the potential of these complementary techniques. Y1 - 2019 U6 - https://doi.org/10.1021/acs.analchem.9b00519 SN - 0003-2700 SN - 1520-6882 VL - 91 IS - 11 SP - 7208 EP - 7214 PB - American Chemical Society CY - Washington ER - TY - GEN A1 - Pischon, Hannah A1 - Radbruch, Moritz A1 - Ostrowski, Anja A1 - Schumacher, Fabian A1 - Hoenzke, Stefan A1 - Kleuser, Burkhard A1 - Hedtrich, Sarah A1 - Fluhr, Joachim W. A1 - Gruber, Achim D. A1 - Mundhenk, Lars T1 - How Effective Is Tacrolimus in the Imiquimod BT - Induced Mouse Model of Psoriasis? T2 - The journal of investigative dermatology Y1 - 2017 U6 - https://doi.org/10.1016/j.jid.2017.09.019 SN - 0022-202X SN - 1523-1747 VL - 138 IS - 2 SP - 455 EP - 458 PB - Elsevier CY - New York ER -